Localization of a novel melanoma susceptibility locus to 1p22

Over the past 20 years, the incidence of cutaneous malignant melanoma (CMM) has increased dramatically worldwide. A positive family history of the disease is among the most established risk factors for CMM; it is estimated that 10% of CMM cases result from an inherited predisposition. Although mutations in two genes, CDKN2A and CDK4, have been shown to confer an increased risk of CMM, they account for only 20%-25% of families with multiple cases of CMM. Therefore, to localize additional loci involved in melanoma susceptibility, we have performed a genomewide scan for linkage in 49 Australian pedigrees containing at least three CMM cases, in which CDKN2A and CDK4 involvement has been excluded. The highest two-point parametric LOD score (1.82; recombination fraction [theta] 0.2) was obtained at D1S2726, which maps to the short arm of chromosome 1 (1p22). A parametric LOD score of 4.65 (theta = 0) and a nonparametric LOD score of 4.19 were found at D1S2779 in nine families selected for early age at onset. Additional typing yielded seven adjacent markers with LOD scores 13 in this subset, with the highest parametric LOD score, 4.95 (theta = 0) ( nonparametric LOD score 5.37), at D1S2776. Analysis of 33 additional multiplex families with CMM from several continents provided further evidence for linkage to the 1p22 region, again strongest in families with the earliest mean age at diagnosis. A nonparametric ordered sequential analysis was used, based on the average age at diagnosis in each family. The highest LOD score, 6.43, was obtained at D1S2779 and occurred when the 15 families with the earliest ages at onset were included. These data provide significant evidence of a novel susceptibility gene for CMM located within chromosome band 1p22.

Localization of the Epstein-Barr virus protein LMP 1 to exosomes

The Epstein-Barr virus latent membrane protein (LMP 1) functions as a constitutively active signalling molecule and associates in lipid rafts clustered with other signalling molecules. Using immunofluorescent confocal microscopy, LMP 1 was shown to have an heterogeneous distribution among individual cells which was not related to the cell cycle stage. LMP 1 was shown to localize to intracellular compartments in cells other than the plasma membrane, Co-labelling of cells with both an LIMP 1 antibody and an antibody to the Golgi protein GS15 revealed that the intracellular LMP 1 partly co-localized with the Golgi apparatus. Further confirmation of intracellular LMP 1 localization was obtained by immunoelectron microscopy with rabbit polyclonal LIMP 1 antibodies and cryosectioning. As well as being present in intracellular foci, LMP 1 co-localized in part with MHC-II and was present on exosomes derived from a lymphoblastoid cell line. Preparations of LMP 1 containing exosomes were shown to inhibit the proliferation of peripheral blood mononuclear cells, suggesting that LIMP 1 could be involved in immune regulation. This may be of particular relevance in EBV-associated tumours such as nasopharyngeal carcinoma and Hodgkin's disease, as LMP 1-containing exosomes may be taken up by infiltrating T-lymphocytes, where LMP 1 could exert an anti-proliferative effect, allowing the tumour cells to evade the immune system.

14-3-3 acts as an intramolecular bridge to regulate cdc25B localization and activity

One of the major regulators of mitosis in somatic cells is cdc25B. cdc25B is tightly regulated at multiple levels. The final activation step involves the regulated binding of 14-3-3 proteins. Previous studies have demonstrated that Ser-323 is a primary 14-3-3 binding site in cdc25B, which influences its activity and cellular localization. 14-3-3 binding to this site appeared to interact with the N-terminal domain of cdc25B to regulate its activity. The presence of consensus 14-3-3 binding sites in the N-terminal domain suggested that the interaction is through direct binding of the 14-3-3 dimer to sites in the N-terminal domain. We have identified Ser-151 and Ser-230 in the N-terminal domain as functional 14-3-3 binding sites utilized by cdc25B in vivo. These low affinity sites cooperate to bind the 14-3-3 dimer bound to the high affinity Ser-323 site, thus forming an intramolecular bridge that constrains cdc25B structure to prevent access of the catalytic site. Loss of 14-3-3 binding to either N-terminal site relaxes cdc25B structure sufficiently to permit access to the catalytic site, and the nuclear export sequence located in the N-terminal domain. Mutation of the Ser-323 site was functionally equivalent to the mutation of all three sites, resulting in the complete loss of 14-3-3 binding, increased access of the catalytic site, and access to nuclear localization sequence.

Human cryptosporidiosis: detection of specific antibodies in the serum by an indirect immunofluorescence

Cryptosporidium sp., a coccidian parasite usually found in the faeces of cattle, has been recently implicated as an agent of human intestinal disease, mainly in immunocompromised patients. In the study realized, by an indirect immunofluorescence technique, specific immunoglobulins (IgG and IgM) have been demonstrated in human serum against Cryptosporidium oocysts. Purified oocysts were used as antigens in the indirect immunofluorecence assay. After analyzing this test in sera from selected groups of patients, the frequency of both specific IgG and IgM of immunocompetent children who were excreting oocysts in their faeces was 62% and in children with negative excretion of oocysts was 20% and 40%, respectively. In adults infected with the human immunodeficiency virus (HIV) and who were excreting Cryptosporidium in their stools, the frequency was 57% for IgG but only 2% for IgM. Twenty three percent of immunocompromised adults with not determined excretion of oocysts in their stools had anti-Cryptosporidium IgG in their sera. Children infected with human immunodeficiency virus had no IgM and only 14% had IgG detectable in their sera. The indirect immunoflorescence assay, when used with other parasitological techniques appears to be useful for retrospective population studies and for diagnosis of acute infection. The humoral immune response of HIV positive patients to this protozoan agent needs clarification.

Performance of microstrip antennas in the presence of EBG in an indoor localization system

Indoor localization systems in nowadays is a huge area of interest not only at academic but also at industry and commercial level. The correct location in these systems is strongly influenced by antennas performance which can provide several gains, bandwidths, polarizations and radiation patterns, due to large variety of antennas types and formats. This paper presents the design, manufacture and measurement of a compact microstrip antenna, for a 2.4 GHZ frequency band, enhanced with the use of Electromagnetic Band-Gap (EBG) structures, which improve the electromagnetic behavior of the conventional antennas. The microstrip antenna with an EBG structure integrated allows an improvement of the location system performance in about 25% to 30% relatively to a conventional microstrip antenna.

Subunits of the chaperonin CCT are associated with Tetrahymena microtubule structures and are involved in cilia biogenesis

The cytosolic chaperonin CCT is a heterooligomeric complex of about 900 kDa that mediates the folding of cytoskeletal proteins. We observed by indirect immunofluorescence that the Tetrahymena TpCCTalpha, TpCCTdelta, TpCCTepsilon, and TpCCTeta-subunits colocalize with tubulin in cilia, basal bodies, oral apparatus, and contractile vacuole pores. TpCCT-subunits localization was affected during reciliation. These findings combined with atomic force microscopy measurements in reciliating cells indicate that these proteins play a role during cilia biogenesis related to microtubule nucleation, tubulin transport, and/or axoneme assembly. The TpCCT-subunits were also found to be associated with cortex and cytoplasmic microtubules suggesting that they can act as microtubule-associated proteins. The TpCCTdelta being the only subunit found associated with the macronuclear envelope indicates that it has functions outside of the 900 kDa complex. Tetrahymena cytoplasm contains granular/globular-structures of TpCCT-subunits in close association with microtubule arrays. Studies of reciliation and with cycloheximide suggest that these structures may be sites of translation and folding. Combined biochemical techniques revealed that reciliation affects the oligomeric state of TpCCT-subunits being tubulin preferentially associated with smaller CCT oligomeric species in early stages of reciliation. Collectively, these findings indicate that the oligomeric state of CCT-subunits reflects the translation capacity of the cell and microtubules integrity.

The Moving Text. Localization, translation and distribution

For some years now, translation theorist and educator Anthony Pym has been trying to establish a dialogue between the academic tradition he comes from and the world of the language industries into which he is meant to introduce his students: in other words, between the Translation Studies discipline and the localisation sector. This rapprochement is also the stated aim of his new book The Moving Text (p. 159). Rather than collect and synthesise what was previously dispersed over several articles, Pym has rewritten his material completely, both literally and conceptually, all in the light of the more than three decades of research he has conducted into the field of cross--cultural communication. The theoretical arguments are ably supported by a few short but telling and well-exploited examples.

An Evaluation of Local Feature Combiners for Robot Visual Localization

In the last decade, local image features have been widely used in robot visual localization. To assess image similarity, a strategy exploiting these features compares raw descriptors extracted from the current image to those in the models of places. This paper addresses the ensuing step in this process, where a combining function must be used to aggregate results and assign each place a score. Casting the problem in the multiple classifier systems framework, we compare several candidate combiners with respect to their performance in the visual localization task. A deeper insight into the potential of the sum and product combiners is provided by testing two extensions of these algebraic rules: threshold and weighted modifications. In addition, a voting method, previously used in robot visual localization, is assessed. All combiners are tested on a visual localization task, carried out on a public dataset. It is experimentally demonstrated that the sum rule extensions globally achieve the best performance. The voting method, whilst competitive to the algebraic rules in their standard form, is shown to be outperformed by both their modified versions.

“Papel dos recetores purinérgicos no crescimento e temodelação do tecido cavernoso”

A adenosina é um nucleósido ubíquo envolvido na regulação de controlo do tónus vascular do tecido cavernoso, desempenhando um papel importante na fisiopatologia da Disfunção Erétil (DE) resistente aos fármacos relaxantes musculares clássicos. Apesar da importância comprovada dos recetores da adenosina na fisiopatologia da DE no homem, pouca informação é conhecida no que diz respeito à expressão e localização dos recetores purinérgicos no Tecido Cavernoso de Ratazana (TCR). Neste trabalho avaliou-se o fenótipo dos recetores purinérgicos responsáveis pela regulação do tónus do tecido erétil de ratazana por imunofluorescência indireta aplicada à microscopia confocal em co-culturas de células endoteliais e musculares lisas do TCR. Para além da caracterização imunofenotípica, desenvolveu-se uma técnica que permite diferenciar funcionalmente em tempo real (por microscopia confocal funcional) células musculares lisas e células endoteliais isoladas de TCR em co-cultura marcadas com a sonda fluorescente Fluo-4NW. Esta técnica permite distinguir cada um dos subtipos celulares mediante o padrão e a magnitude das oscilações dos níveis intracelulares de Ca2+ ([Ca2+]i) em resposta ao ATP (agonista P2) e à fenilefrina (PE, agonista α-adrenérgico). Nas células musculares lisas, observou-se uma resposta mais acentuada ao agonista α-adrenérgico, PE, e uma resposta menos significativa ao ATP. O contrário foi observado relativamente às células endoteliais. A incubação das células musculares lisas e endoteliais com ATP (300 μM) causou um aumento dos níveis de [Ca2+]i. O efeito do ATP (300 μM) parece envolver a ativação de recetores dos subtipos P2X1 e P2X3 sensíveis ao bloqueio com NF023 (3μM) e A317491 (100 nM), respetivamente. Já o aumento dos níveis [Ca2+]i produzido pelo ADP (300 μM) parece envolver a ativação de recetores P2Y1, P2Y12 e P2Y13 mediante o antagonismo produzido pelos antagonistas MRS 2179 (0,3μM), AR-C66096 (0,1 μM) e MRS 2211 (10μM), respetivamente. Os dois tipos celulares expressam imunorreatividade contra recetores A2A, A2B, P2X1, P2X3, P2Y1, P2Y12 e P2Y13.

Taxonomy of fundamental concepts of localization in cyber-physical and sensor networks

Localization is a fundamental task in Cyber-Physical Systems (CPS), where data is tightly coupled with the environment and the location where it is generated. The research literature on localization has reached a critical mass, and several surveys have also emerged. This review paper contributes on the state-of-the-art with the proposal of a new and holistic taxonomy of the fundamental concepts of localization in CPS, based on a comprehensive analysis of previous research works and surveys. The main objective is to pave the way towards a deep understanding of the main localization techniques, and unify their descriptions. Furthermore, this review paper provides a complete overview on the most relevant localization and geolocation techniques. Also, we present the most important metrics for measuring the accuracy of localization approaches, which is meant to be the gap between the real location and its estimate. Finally, we present open issues and research challenges pertaining to localization. We believe that this review paper will represent an important and complete reference of localization techniques in CPS for researchers and practitioners and will provide them with an added value as compared to previous surveys.

Entity localization and tracking: a sensor fusion-based mechanism in WSNs

Knowing exactly where a mobile entity is and monitoring its trajectory in real-time has recently attracted a lot of interests from both academia and industrial communities, due to the large number of applications it enables, nevertheless, it is nowadays one of the most challenging problems from scientific and technological standpoints. In this work we propose a tracking system based on the fusion of position estimations provided by different sources, that are combined together to get a final estimation that aims at providing improved accuracy with respect to those generated by each system individually. In particular, exploiting the availability of a Wireless Sensor Network as an infrastructure, a mobile entity equipped with an inertial system first gets the position estimation using both a Kalman Filter and a fully distributed positioning algorithm (the Enhanced Steepest Descent, we recently proposed), then combines the results using the Simple Convex Combination algorithm. Simulation results clearly show good performance in terms of the final accuracy achieved. Finally, the proposed technique is validated against real data taken from an inertial sensor provided by THALES ITALIA.

Engineering a search and rescue application with a wireless sensor network - based localization mechanism

The advent of Wireless Sensor Network (WSN) technologies is paving the way for a panoply of new ubiquitous computing applications, some of them with critical requirements. In the ART-WiSe framework, we are designing a two-tiered communication architecture for supporting real-time and reliable communications in WSNs. Within this context, we have been developing a test-bed application, for testing, validating and demonstrating our theoretical findings - a search&rescue/pursuit-evasion application. Basically, a WSN deployment is used to detect, localize and track a target robot and a station controls a rescuer/pursuer robot until it gets close enough to the target robot. This paper describes how this application was engineered, particularly focusing on the implementation of the localization mechanism.

A lightweight indoor localization model based on motley-keenan and COST

This paper presents a novel approach to WLAN propagation models for use in indoor localization. The major goal of this work is to eliminate the need for in situ data collection to generate the Fingerprinting map, instead, it is generated by using analytical propagation models such as: COST Multi-Wall, COST 231 average wall and Motley- Keenan. As Location Estimation Algorithms kNN (K-Nearest Neighbour) and WkNN (Weighted K-Nearest Neighbour) were used to determine the accuracy of the proposed technique. This work is based on analytical and measurement tools to determine which path loss propagation models are better for location estimation applications, based on Receive Signal Strength Indicator (RSSI).This study presents different proposals for choosing the most appropriate values for the models parameters, like obstacles attenuation and coefficients. Some adjustments to these models, particularly to Motley-Keenan, considering the thickness of walls, are proposed. The best found solution is based on the adjusted Motley-Keenan and COST models that allows to obtain the propagation loss estimation for several environments.Results obtained from two testing scenarios showed the reliability of the adjustments, providing smaller errors in the measured values values in comparison with the predicted values.

Localization studies of the FemXAB protein family in Staphylococcus aureus

Dissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

2D PCA-Based localization for mobile robots in unstructured environments

In this paper a new PCA-based positioning sensor and localization system for mobile robots to operate in unstructured environments (e. g. industry, services, domestic ...) is proposed and experimentally validated. The inexpensive positioning system resorts to principal component analysis (PCA) of images acquired by a video camera installed onboard, looking upwards to the ceiling. This solution has the advantage of avoiding the need of selecting and extracting features. The principal components of the acquired images are compared with previously registered images, stored in a reduced onboard image database, and the position measured is fused with odometry data. The optimal estimates of position and slippage are provided by Kalman filters, with global stable error dynamics. The experimental validation reported in this work focuses on the results of a set of experiments carried out in a real environment, where the robot travels along a lawn-mower trajectory. A small position error estimate with bounded co-variance was always observed, for arbitrarily long experiments, and slippage was estimated accurately in real time.